作者
Irena Štefanová, Bernhard Hemmer, Marco Vergelli, Roland Martin, William E Biddison, Ronald N Germain
发表日期
2003/3/1
期刊
Nature immunology
卷号
4
期号
3
页码范围
248-254
出版商
Nature Publishing Group US
简介
Functional discrimination between structurally similar self and foreign antigens is a main attribute of adaptive immunity. Here we describe two feedback mechanisms in T lymphocytes that together sharpen and amplify initial signaling differences related to the quality of T cell receptor (TCR) engagement. Weakly binding ligands predominantly trigger a negative feedback loop leading to rapid recruitment of the tyrosine phosphatase SHP-1, followed by receptor desensitization through inactivation of Lck kinase. In contrast, strongly binding ligands efficiently activate a positive feedback circuit involving Lck modification by ERK, preventing SHP-1 recruitment and allowing the long-lasting signaling necessary for gene activation. The characteristics of these pathways suggest that they constitute an important part of the mechanism allowing T cells to discriminate between self and foreign ligands.
引用总数
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TCR ligand discrimination is enforced by competing ERK positive and SHP-1 negative feedback pathways
I Štefanová, B Hemmer, M Vergelli, R Martin… - Nature immunology, 2003